SSADH
MCID: SCC001
MIFTS: 50

Succinic Semialdehyde Dehydrogenase Deficiency (SSADH) malady

Genetic diseases, Rare diseases, Neuronal diseases categories
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Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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8Disease Ontology, 21Genetics Home Reference, 43NIH Rare Diseases, 65Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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Genetics Home Reference:21 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to wagr syndrome and juvenile absence epilepsy, and has symptoms including organic acid metabolism anomalies, psychic/behavioural troubles and hypotonia. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (aldehyde dehydrogenase 5 family, member A1), and among its related pathways are Arginine and proline metabolism and Neurotransmitter Release Cycle. The compounds Succinic acid semialdehyde and vigabatrin have been mentioned in the context of this disorder. Affiliated tissues include globus pallidus, brain and liver.

Disease Ontology:8 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:43 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

Wikipedia:65 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

Description from OMIM:47 271980

GeneReviews summary for ssadh

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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8Disease Ontology, 9diseasecard, 19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 47OMIM, 10DISEASES, 49Orphanet, 62UMLS, 59SNOMED-CT via Orphanet, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

49
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood


Aliases & Descriptions:

succinic semialdehyde dehydrogenase deficiency 8 9 19 43 21 47 10 49 62
4-hydroxybutyric aciduria 8 19 43 21 49
gamma-hydroxybutyric aciduria 8 19 21
ssadh deficiency 19 43 21
succinic semialdehyde dehydrogenase 9 20
gamma-hydroxybutyric acidemia 21
gamma-hydroxybutyricaciduria 43
4-hydroxybutyricaciduria 21
gaba metabolic defect 43
ssadh 8


External Ids:

Disease Ontology8 DOID:0060175
SNOMED-CT via Orphanet59 49748000
OMIM47 271980
ICD10 via Orphanet26 E72.8

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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17GeneCards, 18GeneDecks
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Diseases related to Succinic Semialdehyde Dehydrogenase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 16)
idRelated DiseaseScoreTop Affiliating Genes
1wagr syndrome30.7WT1
2juvenile absence epilepsy10.4
3canavan disease10.4
4neuroleptic malignant syndrome10.4
5dystonia10.4
6intellectual disability10.4
7obesity10.4
8sleep disorder10.4
9mental retardation10.4
10hypotonia10.4
11status epilepticus10.3
12idiopathic generalized epilepsy10.3
13williams syndrome10.3
14dysequilibrium syndrome10.3
15d-2-hydroxyglutaric aciduria10.1
16homocarnosinosis10.0ALDH5A1, ABAT

Graphical network of diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Symptoms for Succinic Semialdehyde Dehydrogenase Deficiency

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47OMIM, 49Orphanet
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Symptoms by clinical synopsis from OMIM:

271980

Clinical features from OMIM:

271980

Symptoms:

49 (show all 7)
  • organic acid metabolism anomalies
  • psychic/behavioural troubles
  • hypotonia
  • ataxia/incoordination/trouble of the equilibrium
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • seizures/epilepsy/absences/spasms/status epilepticus
  • autosomal recessive inheritance

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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42NIH Clinical Center, 6ClinicalTrials
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Drug clinical trials:

Search ClinicalTrials for Succinic Semialdehyde Dehydrogenase Deficiency

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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20GeneTests
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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinic Semialdehyde Dehydrogenase Deficiency20 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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33MalaCards
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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

33
Globus pallidus, Brain, Liver

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

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Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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52PubMed
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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 60)
idTitleAuthorsYear
1
Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. (23430529)
2013
2
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
3
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
4
A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. (23825041)
2013
5
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
6
A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. (22437753)
2012
7
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
8
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
9
Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. (19896403)
2010
10
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
11
Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin]. (20018576)
2010
12
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
13
Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. (19172412)
2009
14
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
15
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
16
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
17
Clinical, cytogenetic and molecular characterization of a patient with combined succinic semialdehyde dehydrogenase deficiency and incomplete WAGR syndrome with obesity. (16545979)
2006
18
Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. (16542398)
2006
19
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
20
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
21
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
22
The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. (15059623)
2004
23
Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). (15341910)
2004
24
Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency. (12829002)
2003
25
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
26
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
27
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
28
Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography-mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency. (12127325)
2002
29
Selective involvement of the globus pallidus and dentate nucleus in succinic semialdehyde dehydrogenase deficiency. (12136353)
2002
30
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
31
A unique mouse model for succinic semialdehyde dehydrogenase deficiency with implications for gamma hydroxybutyrate intoxication. (11990378)
2002
32
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
33
Succinic semialdehyde dehydrogenase deficiency in siblings: clinical heterogeneity and response to early treatment. (10234622)
1999
34
Two exon-skipping mutations as the molecular basis of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9683595)
1998
35
4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. (9553943)
1998
36
Unusual enzyme findings in five patients with metabolic profiles suggestive of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9686370)
1998
37
The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. (9093300)
1997
38
Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate. (9061565)
1997
39
Differing clinical presentation of succinic semialdehyde dehydrogenase deficiency in adolescent siblings from Lifu Island, New Caledonia. (9266358)
1997
40
Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). (8803774)
1996
41
Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. (7564230)
1995
42
Pre- and postnatal diagnosis of succinic semialdehyde dehydrogenase deficiency using enzyme and metabolite assays. (7707697)
1994
43
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
44
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
45
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
46
Vigabatrin therapy in patient with succinic semialdehyde dehydrogenase deficiency. (2572834)
1989
47
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. (3126356)
1987
48
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
49
Succinic semialdehyde dehydrogenase deficiency. (6536727)
1984
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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64UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

64 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203
6ALDH5A1p.Gly268GluVAR_026204
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210

Clinvar genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

1
id Gene Name Type Significance SNP ID Assembly Location
1ALDH5A1ALDH5A1, IVS9, G-T, +1single nucleotide variantPathogenic
2ALDH5A1ALDH5A1, IVS5, G-A, +1single nucleotide variantPathogenic
3ALDH5A1NM_170740.1(ALDH5A1): c.612G> A (p.Trp204Ter)single nucleotide variantPathogenicrs118203982GRCh37Chr 6, 24505099: 24505099
4ALDH5A1NM_170740.1(ALDH5A1): c.1273C> T (p.Arg425Ter)single nucleotide variantPathogenicrs118203983GRCh37Chr 6, 24528285: 24528285
5ALDH5A1NM_170740.1(ALDH5A1): c.1265G> A (p.Gly422Asp)single nucleotide variantPathogenicrs118203984GRCh37Chr 6, 24528277: 24528277
6ALDH5A1NG_008161.1: g.31299_33753deldeletionPathogenicGRCh37Chr 6, 24521495: 24523949

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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2BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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50PathCards, 30KEGG, 55Reactome, 38NCBI BioSystems Database, 51PharmGKB
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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
citrulline-nitric oxide cycle38
arginine degradation I (arginase pathway)38
proline degradation38
glutamine degradation I38
proline biosynthesis I38
superpathway of citrulline metabolism38
proline biosynthesis II (from arginine)38
citrulline biosynthesis38
arginine degradation VI (arginase 2 pathway)38
Urea cycle and metabolism of amino groups38
asparagine biosynthesis I38
4-hydroxyproline degradation I38
citrulline degradation38
9.5ALDH1B1, ALDH4A1
2
Show member pathways
9.5ABAT, ALDH5A1
3
Show member pathways
9.5ABAT, ALDH5A1
4
Show member pathways
aspartate biosynthesis38
9.5ABAT, ALDH5A1
59.0ALDH4A1, ALDH5A1, ABAT
6
Show member pathways
beta-alanine degradation I38
valine degradation I38
pyruvate fermentation to lactate38
isoleucine degradation I38
8.8ABAT, ALDH6A1, ALDH1B1
7
Show member pathways
phenylethylamine degradation I38
8.8ABAT, ALDH6A1, ALDH1B1
8
Show member pathways
8.0ALDH5A1, ALDH1B1, ALDH6A1, ALDH4A1, ABAT

Compounds for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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24HMDB, 29IUPHAR, 45Novoseek, 11DrugBank, 61Tocris Bioscience, 3BitterDB, 51PharmGKB
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Compounds related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 24)
idCompoundScoreTop Affiliating Genes
1Succinic acid semialdehyde249.8ALDH5A1, ABAT
2vigabatrin29 45 1111.8ABAT, ALDH5A1
3vitamin b6459.7ALDH5A1, ABAT
4Malonic semialdehyde249.7ALDH6A1, ABAT
5alpha-ketoglutarate459.7ALDH5A1, ABAT
62-Methyl-3-oxopropanoic acid249.6ALDH6A1, ABAT
7succinate459.6ABAT, ALDH5A1
8beta-alanine45 61 29 24 1113.6ALDH1B1, ABAT
9Gamma-Aminobutyric acid249.6ALDH1B1, ABAT
10famotidine45 3 24 1112.6ALDH4A1, ABAT
11valproic acid45 51 24 1112.5ALDH5A1, ABAT
12l-glutamic acid29 24 1111.5ALDH4A1, ABAT
13NADP249.5ALDH1B1, ALDH4A1
14succinic semialdehyde459.4ALDH5A1, AKR7A2, ABAT
15gamma-hydroxybutyrate459.4ABAT, AKR7A2, ALDH5A1
16taurine45 61 2411.3ABAT, WT1
17(S)-Methylmalonic acid semialdehyde249.2ALDH1B1, ALDH6A1, ABAT
18nadph45 2410.1ALDH1B1, ALDH4A1, ABAT
19ornithine45 2410.0WT1, ABAT
20Water249.0ALDH4A1, ALDH5A1, ALDH1B1
21nad29 249.9ALDH1B1, ALDH5A1, ALDH4A1, ALDH6A1
22nadh45 24 1110.9ALDH6A1, ALDH4A1, ALDH5A1, ALDH1B1
23glutamine458.9ABAT, ALDH5A1, WT1
24glutamate458.7ALDH5A1, ALDH4A1, ABAT

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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16Gene Ontology
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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrionGO:0057398.4ALDH1B1, ALDH5A1, ALDH6A1, ABAT
2mitochondrial matrixGO:0057597.7ALDH1B1, ALDH5A1, ALDH4A1, ALDH6A1, ABAT

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1neurotransmitter secretionGO:0072699.5ALDH5A1, ABAT
2gamma-aminobutyric acid catabolic processGO:0094509.4ALDH5A1, ABAT
3neurotransmitter catabolic processGO:0421359.2ALDH5A1, ABAT

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1electron carrier activityGO:0090559.6ALDH4A1, AKR7A2
2aldehyde dehydrogenase (NAD) activityGO:0040299.2ALDH1B1, ALDH4A1

Products for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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4CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
59SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet